Alterations of the Blood-Brain Barrier and Regional Perfusion in Tumor Development: MRI Insights from a Rat C6 Glioma Model.

Monika Huhndorf,Olga Will,Nadine Kramann,Christine Stadelmann,Kirsten Hattermann,Olav Jansen,Amir Moussavi,Susann Boretius

doi:10.1371/journal.pone.0168174

Abstract

ObjectivesAngiogenesis and anti-angiogenetic medications play an important role in progression and therapy of glioblastoma. In this context, in vivo characterization of the blood-brain-barrier and tumor vascularization may be important for individual prognosis and therapy optimization.MethodsWe analyzed perfusion and capillary permeability of C6-gliomas in rats at different stages of tumor-growth by contrast enhanced MRI and dynamic susceptibility contrast (DSC) MRI at 7 Tesla. The analyses included maps of relative cerebral blood volume (CBV) and signal recovery derived from DSC data over a time period of up to 35 days after tumor cell injections.ResultsIn all rats tumor progression was accompanied by temporal and spatial changes in CBV and capillary permeability. A leakage of the blood-brain barrier (slow contrast enhancement) was observed as soon as the tumor became detectable on T2-weighted images. Interestingly, areas of strong capillary permeability (fast signal enhancement) were predominantly localized in the center of the tumor. In contrast, the tumor rim was dominated by an increased CBV and showed the highest vessel density compared to the tumor center and the contralateral hemisphere as confirmed by histology.ConclusionSubstantial regional differences in the tumor highlight the importance of parameter maps in contrast or in addition to region-of-interest analyses. The data vividly illustrate how MRI including contrast-enhanced and DSC-MRI may contribute to a better understanding of tumor development.

Highlights

Glioblastoma multiforme (GM) is one of the most malignant and frequent primary brain tumors [1]
A leakage of the blood-brain barrier was observed as soon as the tumor became detectable on T2-weighted images
The tumor rim was dominated by an increased cerebral blood volume (CBV) and showed the highest vessel density compared to the tumor center and the contralateral hemisphere as confirmed by histology

Summary

Introduction

Glioblastoma multiforme (GM) is one of the most malignant and frequent primary brain tumors [1]. Tumor-driven angiogenesis and inflammation are often accompanied by increased capillary permeability. This is detected by contrast agents such as Gd-DTPA passing into the extravascular space. Compared to the initial intravascular bolus, the concentration of the extravascular contrast agent is significantly lower and increases slowly over time leading to a signal enhancement on T1-weighted images. This effect is utilized by dynamic contrastenhanced (DCE) MRI [7, 8]

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